Sjögren's Syndrome (SS) is a systemic autoimmune disease with a prevalence of 1-3%, affecting more women than men with a ratio of 9:1. It is characterized by chronic focal leukocyte infiltration and inflammation of exocrine glands, primarily involving salivary (and lacrimal) glands thereby resulting in persistence dryness of the mouth (and eyes). Primary SS occurs independent of another autoimmune disease while secondary SS occurs against a background of other connective tissue diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus). The serological hallmark of SS is the presence of circulating autoantibodies against soluble nuclear RNA containing antigens, Ro/SSA and La/SSB (Tzioufas, et al., J Autoimmun., 39(1-2):4-8 (2012); Seror, et al., J Autoimmun., 39(1-2):97-102 (2012); Mathews, et al., J Dent Res, 87(4): 308-318 (2008)).
The pathogenesis of SS remains poorly understood but hallmark histopathological findings of the disease include perivascular and periductal leukocyte infiltration of exocrine glands and associated inflammation (Tzioufas, et al., J Autoimmun., 39(1-2):4-8 (2012); Seror, et al., J Autoimmun., 39(1-2):97-102 (2012); Mathews, et al., J Dent Res, 87(4): 308-318 (2008); Abdulahad, et al., J. Autoimmun., 39(1-2):103-11 (2012); Singh, et al., J Autoimmun., 39(3:229-33 (2012); Roescher, et al., Oral Dis., 18(1):96-106 (2012); Moriyama, et al., Clin Exp Immunol., 169(1):17-26 (2012)). One potential mechanism for leukocyte infiltration could relate to dysregulation of recently discovered endogenous inhibitors of leukocyte adhesion. Prominent among them is the developmental endothelial locus-1 (Del-1) which has emerged as an important player in pathogenesis of several conditions including periodontitis (Chavakis, et al., Eur J Clin Invest., 42(6):686-91 (2012); Choi, et al., Immune Netw., 9(5):153-7 (2009); Eskan, et al., Nat Immunol., 13(5):465-73 (2012)). Aside from the contribution of systemic immune and inflammatory mechanisms, mounting evidence supports a pivotal role for the endoplasmic reticulum (ER) stress response in regulating endogenous cellular inflammatory mechanisms and cell death (Johnson, et al., Curr Pharm Des., 17, 284-292 (2012); Liu, et al., Biochem. Biophys. Res. Commun., 370, 651-656 (2008); Mondal, et al., Metab. Syndr. Relat. Disord., 10, 297-306 (2012); Cunard, Am. J. Physiol. Renal. Physiol., 300, F1054-F1061 (2011); Baban, et al., Hypertension. 61(1):95-104 (2013); Baban, et al., Exp Mol Pathol., doi:pii: S0014-4800(12)00175-X. 10.1016/j.yexmp 0.2012.11.004 [Epub ahead of print] (2012); Miyazaki, et al., Arterioscler Thromb Vasc Biol, 31(5):1124-32 (2011); Hasnain, et al., Immunol. Cell. Biol., 90, 260-70 (2012)). Importantly, the status of ER stress response and potential role of Del-1 in pathogenesis of salivary gland impairment in SS are not established.
Therefore, it is an objection of the invention to provide compositions and methods for detecting, diagnosing, and monitoring the progression of SS.
It is also an object of the invention to provide compositions and methods for treating SS.
It is a further object of the invention to provide methods of monitoring the effectiveness of SS treatment.